title: Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience.
abstract: Animal models and human functional imaging data implicate the dopamine system in mediating enhanced encoding of novel stimuli into human memory. A separate line of investigation suggests an association between a functional polymorphism in the promoter region for the human dopamine 4 receptor gene (DRD4) and sensitivity to novelty. We demonstrate, in two independent samples, that the -521C>T DRD4 promoter polymorphism determines the magnitude of human memory enhancement for contextually novel, perceptual oddball stimuli in an allele dose-dependent manner. The genotype-dependent memory enhancement conferred by the C allele is associated with increased neuronal responses during successful encoding of perceptual oddballs in the ventral striatum, an effect which is again allele dose-dependent. Furthermore, with repeated presentations of oddball stimuli, this memory advantage decreases, an effect mirrored by adaptation of activation in the hippocampus and substantia nigra/ventral tegmental area in C carriers only. Thus, a dynamic modulation of human memory enhancement for perceptually salient stimuli is associated with activation of a dopaminergic-hippocampal system, which is critically dependent on a functional polymorphism in the DRD4 promoter region.
authors.affiliation: Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Laboratory for Clinical Neuroscience, Centre for Biomedical Technology, Technical University of Madrid, Spain. Electronic address: bryan.strange@upm.es.
authors.forename: B A
authors.initials: BA
authors.lastname: Strange
authors.forename: N
authors.initials: N
authors.lastname: Gartmann
authors.forename: J
authors.initials: J
authors.lastname: Brenninkmeyer
authors.forename: J
authors.initials: J
authors.lastname: Haaker
authors.forename: A
authors.initials: A
authors.lastname: Reif
authors.forename: R
authors.initials: R
authors.lastname: Kalisch
authors.forename: C
authors.initials: C
authors.lastname: Büchel
mesh_terms: D000328:Adult; D001921:Brain / Q000502:physiology*; D004298:Dopamine / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D055815:Young Adult
chemical_list: C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4; D004298:Dopamine
keywords: DRD4 promoter polymorphism; Dopamine; Hippocampus; Memory; Novelty; fMRI